• Title/Summary/Keyword: oxidative DNA damage

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Molecular Mechanism of Tetrabromobisphenol A (TBBPA)-induced Target Organ Toxicity in Sprague-Dawley Male Rats

  • Choi, Jae-Seok;Lee, Young-Jun;Kim, Tae-Hyung;Lim, Hyun-Jung;Ahn, Mee-Young;Kwack, Seung-Jun;Kang, Tae-Seok;Park, Kui-Lea;Lee, Jae-Won;Kim, Nam-Deuk;Jeong, Tae-Cheon;Kim, Sang-Geum;Jeong, Hye-Gwang;Lee, Byung-Mu;Kim, Hyung-Sik
    • Toxicological Research
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    • v.27 no.2
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    • pp.61-70
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    • 2011
  • Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.

Induction of Metallothionein Gene by Laminin in Normal and Malignant Human Prostate Epithelial Cells (악성 단계별 인간 전립선 암세포에서 라미닌에 의한 metallothionein 유전자 발현유도 현상 연구)

  • Ock, Mee-Sun;Cha, Hee-Jae
    • Journal of Life Science
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    • v.21 no.4
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    • pp.529-533
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    • 2011
  • Metallothioneins (MT) are a group of low-molecular weight, cysteine-rich, intracellular proteins that are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins is associated with protection against DNA damage, oxidative stress, and apoptosis. Many studies have shown increased expression of MT in various human tumors, whereas MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. Using Northern blot analysis, we found that laminin induced expression of MT-1 in HSG and PC12 cells, which can be differentiated by laminin, but had no effect on MB-231, MDA-435, and PC-3 cells, which cannot be differentiated by laminin. In addition, we analyzed the expression level of the MT-1 gene in five prostate cancer cell lines possessing different metastatic potential. The expression of MT-1 in normal and less malignant cells (RWPE-1 and WPE1-NA22) was high and up-regulated by laminin, whereas the expression of MT-1 in WPE1-NB14, WPE1-NB11, and WPE1-NB26 cells (malignant) was extremely low and not elevated by laminin. These results suggest that the MT-1 gene is involved in laminin-mediated differentiation and affects the metastatic potential of tumor cells.

Antioxidative Activity of Cornus officianalis Extracts Obtained by Four Different Extraction Techniques (산수유 추출방법에 따른 항산화 기능 분석)

  • Park, Eun-Bi;Kim, Hye-Sun;Shin, So-Yun;Ji, In-Ae;Kim, Ji-Hyun;Kim, Sung-Goo;Yoo, Byung Hong;Kim, Byung-Woo;Kwak, Inseok;Kim, Moon-Moo;Chung, Kyung Tae
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1507-1514
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    • 2012
  • Oxidative stress leads to damage in all components of the cell, including proteins, lipids, and DNA due to imbalance between reactive oxygen species production and cellular detoxification. Phytochemicals are well-known to contain antioxidants, and their physiological role has been intensively studied. The fruit of Cornus officianalis has been used in oriental medicine and has been reported to have many functions. In this study, four different extraction techniques were applied to extract functional components from the fruit of Cornus officianalis, and the content of loganin, which is an antioxidant having DPPH radical and hydrogen peroxide scavenging activity and reducing power, was analyzed in each extract. Extraction techniques employed in this study were heat extraction by water, 70% ethanol extraction, enzyme treatment, and combination of enzyme treatment and heat extraction by water. All extracts contained 11.8-18.0 mg/g loganin and showed antioxidation function assayed by measuring DPPH radical and hydrogen peroxide scavenging activity and reducing power. Among them, heat extraction was the most effective technique, showing a maximum amount of loganin (18.0 mg/g) and antioxidative activity at 100 mg/ml concentration. Each extract showed very low cytotoxicity up to at 500 mg/ml but 10-20% cytotoxicity at 1,000 mg/ml by in vitro MTT assay.

Effect of Onion Consumption on Cardiovascular Disease in Human Intervention Studies: A Literature Review (국내.외 인체중재연구를 통해 살펴 본 양파의 심혈관계 질환 개선효과에 관한 고찰)

  • Kim, Jung-Mi;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.10
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    • pp.1565-1572
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    • 2010
  • Onion (Allium cepa L.) production in Korea has increased gradually over the past 15 years, placing second in food consumption survey with 20.6 g daily intake in 2006. Onions, used as an ingredient in many dishes and accepted by almost all traditions and cultures, have been reported to have a range of health benefits which include anticarcinogenic, antiasthmatic, antibiotic, and antioxidative effects. These effects may be attributable to a powerful flavonoid pigment-containing compounds, such as quercetin and alk(en)yl cysteine sulphoxides (ACSOs). Although antiplatelet and antithrombotic activities of onion have been confirmed by many of in vitro or animal studies, only a few human intervention studies have been examined. The majority of human studies identified that onion improves some cardiovascular markers such as lipid profile and platelet coagulant. With regard to antioxidative effects, somewhat positive effects are confirmed through strengthening the resistance of oxidative DNA damage in lymphocyte and urine, while most studies failed to find inhibitory effects on LDL oxidation. The discrepancies among studies might be ascribed to producing area, processing methods of onion, dosage, subject characteristics, study duration, and measurement methods. In this review, we focused on the preventive effect of cardiovascular disease through onion consumption in human intervention studies.

Transition Metal Induces Apoptosis in MC3T3E1 Osteoblast: Evidence of Free Radical Release

  • Chae, Han-Jung;Chae, Soo-Wan;Kang, Jang-Sook;Yun, Dong-Hyeon;Bang, Byung-Gwan;Kang, Mi-Ra;Kim, Hyung-Min;Kim, Hyung-Ryong
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.1
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    • pp.47-54
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    • 2000
  • Transition metal ions including $Se^{2+},\;Cd^{2+},\;Hg^{2+}\;or\;Mn^{2+}$ have been thought to disturb the bone metabolism directly. However, the mechanism for the bone lesion is unknown. In this study, we demonstrated that MC3T3E1 osteoblasts, exposed to various transition metal ions; selenium, cadmium, mercury or manganese, generated massive amounts of reactive oxygen species (ROS). The released ROS were completely quenched by free radical scavengers-N-acetyl cysteine (NAC), reduced glutathione (GSH), or superoxide dismutase (SOD). First, we have observed that selenium $(10\;{\mu}M),$ cadmium $(100\;{\mu}M),$ mercury $(100\;{\mu}M)$ or manganese (1 mM) treatment induced apoptotic phenomena like DNA fragmentation, chromatin condensation and caspase-3-like cysteine protease activation in MC3T3E1 osteoblasts. Concomitant treatment of antioxidant; N-acetyl-L-cysteine (NAC), reduced-form glutathione (GSH), or superoxide dismutase (SOD), prevented apoptosis induced by each of the transition metal ions. Catalase or dimethylsulfoxide (DMSO) has less potent inhibitory effect on the apoptosis, compared with NAC, GSH or SOD. In line with the results, nitroblue tetrazolium (NBT) stain shows that each of the transition metals is a potent source of free radicals in MC3T3E1 osteoblast. Our data show that oxidative damage is associated with the induction of apoptosis in MC3T3E1 osteoblasts following $Se^{2+},\;Cd^{2+},\;Hg^{2+}\;or\;Mn^{2+}$ treatment.

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Effects of Fermentation on the Metabolic Activities of Pine Needle Juice (발효과정이 솔잎 착즙액의 항산화, alpha-Glucosidase 및 Angiotensin Converting Enzyme 저해 활성에 미치는 영향)

  • Kim, So-Yun;Lee, Hyun-Jung;Park, Jae-Hee;Kim, Rae-Young;Cheong, Hyeonsook;Park, Eunju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.3
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    • pp.325-334
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    • 2013
  • The objective of this study was to compare the content and metabolic activities between fresh pine needle juice (PNJ) and fermented pine needle juice (FPNJ). A variety of factors were measured, including total phenolic content (TPC), antioxidant activity [DPPH radical scavenging activity (RSA), total radical-trapping antioxidant potential (TRAP), oxygen radical absorbance capacity (ORAC), cellular antioxidant capacity (CAC)], anti-genotoxic activity, ${\alpha}$-glucosidase inhibitory activity, and angiotensin converting enzyme (ACE) inhibitory activity. The TPC was $17.3{\pm}0.2$ and $4.6{\pm}0.0$ mg GAE/g in PNJ and FPNJ, respectively. The DPPH RSA, TRAP, and ORAC values increased in a dose-dependent manner for both PNJ and FPNJ, with significantly higher activities in PNJ than FPNJ. The CAC against AAPH-induced oxidative stress in HepG2 cells was protected by both PNJ and FPNJ. Pretreatment with PNJ and FPNJ in human leukocytes produced significant reductions in $H_2O_2$-induced DNA damage at a concentration of $50{\mu}g/mL$. ${\alpha}$-Glucosidase inhibitory activity was significantly higher in FPNJ than PNJ. The ACE inhibitory activity was about 87.1% and 60.0% in 1:1 diluted PNJ and FPNJ, respectively. This study suggests that the fermentation of PNJ could enhance the regulation of blood glucose metabolism and both PNJ and FPNJ might be a new potential source of natural antioxidant, anti-diabetic, and anti-hypertensive agents applicable to food.

Effects of Unripened Cheese Supplements on Lipid and Antioxidant Status in Hypercholesterolemic SD Rats (고콜레스테롤혈증 흰쥐에서 비숙성치즈의 보충섭취가 지질 및 항산화 체계에 미치는 영향)

  • Seo, Bo-Young;Spengler, Bernhard;Rompp, Andreas;Schober, Yvonne;Yoon, Yoe-Chang;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.1
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    • pp.65-72
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    • 2012
  • The aim of this study was to evaluate the effects of unripened cheese supplements on lipid metabolism and antioxidant status in hypercholesterolemic SD rats. Rats were induced to have hypercholesterolemia by feeding them high cholesterol diet (0.5% cholesterol and 0.2% sodium cholate) for 4 weeks and then divided into 2 groups. One group was fed a high cholesterol diet with 5% unripened cheese (URC) daily for 6 weeks, and the other one was fed a high cholesterol diet without 5% unripened cheese (URC) daily for 6 weeks. Significantly-increased plasma total cholesterol (TC), triglycerides (TG), and AST activity because of the high-cholesterol diet were reduced 18.8%, 40.5%, and 33%, respectively, by URC supplementation. Also, URC lowered hepatic total lipids, TCs, and TGs, whereas fecal lipid profiles were not changed by URC. The supplementation of URC resulted in an increase of plasma retinol and ${\alpha}$-tocopherol by 40.5% and 39.2% and leukoytic DNA resistance to oxidative stress by 52.3% compared to hypercholesterolemic control. These results suggest that unripened cheese supplements could exert significant health benefits to those with hypercholesterolemia through ameliorating lipid profiles and antioxidant effects.

Antidiabetic Effect of Korean Red Ginseng by Puffing Process in Streptozotocin-Induced Diabetic Rats (Streptozotocin 유발 당뇨쥐에서 팽화가공 처리한 홍삼의 항당뇨 효과)

  • Kim, Shin-Hee;Kang, Ju-Seop;Lee, Sang-Jun;Chung, Young-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.6
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    • pp.701-707
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    • 2008
  • Antidiabetic effect of Korean red ginseng (RG) processed by puffing in streptozotocin (STZ)-induced diabetic (DM) rats was investigated. Five week-old SD rats were divided into four groups; normal control (NC) group, DM group, red ginseng (RG) group and puffed red ginseng (PG) group. The RG and PG groups were orally provided with RG or PG dissolved in water (500 mg/kg) respectively for seven weeks after single injection of STZ (50 mg/kg, i.v.) followed by identification of DM. NC group received saline vehicle instead of STZ. At the end of feeding of RG or PG, the changes of fasting blood glucose, serum insulin and amylase level and serum lipid profiles were evaluated. Also, oral glucose tolerance test (OGTT), comet assay and histopathological examination were performed. At 7th week, the fasting blood glucose levels of the RG and PG groups were reduced compared to the DM group by 11.54% and 20.22%, respectively. The result of OGTT did not show significant differences among DM and two red ginseng groups. While serum insulin and TG levels were predominantly improved in PG group (p<0.05), serum amylase level was increased in RG group. Alkaline comet assay for checking the oxidative damage of DNA showed that TL (tail length, ${\mu}m$) and TM (tail moment) in the blood lymphocyte of PG group significantly decreased in contrast with DM group. Histopathological results of pancreas showed that destruction of exocrine as well as endocrine might be cured by the administration of RG and PG. These results suggest that PG could exert more protection against STZ-induced toxicity than RG group.

Inhibitory Effect of Hot-Water Extract of Paeonia japonica on Oxidative Stress and Identification of Its Active Components (백작약 열수추출물의 산화적 스트레스 억제효과 및 유효성분 동정)

  • Jeong, Ill-Yun;Lee, Joo-Sang;Oh, Heon;Jung, U-Hee;Park, Hae-Ran;Jo, Sung-Kee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.5
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    • pp.739-744
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    • 2003
  • This study was carried out to investigate the antioxidative activity and to identify the active components of hot-water extract of Paeoniajaponica (PJ), which was a main ingredient of a herb mixture preparation recently established as a potent candidate of radioprotector in our laboratory. The water extract was fractionated with CHCl$_3$, EtOAc and n-BuOH. The extract and its fractions showed very low activity in hydroxyl radical scavenging test. In lipid peroxidation test, the extract, EtOAc and water fractions showed moderate inhibition with the ratio above 50%. In DPPH radical scavenging test, the extract, EtOAc and water fraction showed high activity with the ratio above 80%, especially. EtOAc fraction scavenged the radicals as much as synthetic antioxidant (BHA), even at low concentration. It is suggested that mai or partition for antioxidative activity of Paeonia japonica was EtOAc fraction. Subsequently, two active compounds (PJE021-1 and JE024-1) from EtOAc fraction were isolated by using MCI gel and silica gel column chromatography The two compounds inhibited remarkedly the $H_2O$$_2$-induced DNA damage in human peripheral blood lymphocytes, measured by single-cell gel electrophoresis (SCGE). PJE021-1 protected the cells to almost negative control level, dose-dependently. PJE024-1 exhibited a potent inhibition with the ratio of 71% at even low concentration (0.5 $\mu\textrm{g}$/$m\ell$). Finally, their chemical structures were identified as gallic acid (PJE021-1) and (+)-catechin (PJE024-1), respectively, on the basis of the speculation of spectral and physical data.

Effect of Pumpkin, Corn Silk, Adzuki Bean, and Their Mixture on Weight Control and Antioxidant Activities in High Fat Diet-Induced Obesity Rats (호박즙, 옥수수수염차, 팥차 및 혼합물이 식이유도 비만동물모델에서 체중과 항산화 활성에 미치는 영향)

  • Park, Jae-Hee;Lee, Eunji;Park, Eunju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.9
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    • pp.1239-1248
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    • 2016
  • Pumpkin juice (PJ), corn silk tea (CT), and adzuki bean tea (AT) have long been used for treatment of obesity in Korea. This study investigated the efficacy of PJ, CT, AT, and their mixture (PCA) on alteration of body weight and antioxidant metabolism in high-fat diet (HFD)-induced obese rats. After being fed HFD for 4 weeks, SD rats were divided into six groups fed a normal diet (ND), HFD, HFD+PJ [250 mg/kg body weight (BW)], HFD+CT (250 mg/kg BW), HFD+AT (250 mg/kg BW), and HFD+PCA (PJ : CT : AT=1:1:1, 250 mg/kg BW) for another 9 weeks. HFD consumption resulted in total lipid, triglyceride, and total cholesterol accumulation in adipose tissue, which was reduced by administration of PJ, CT, AT, or PCA. The plasma oxygen radical absorbance capacity value and hepatic glutathione peroxidase activity significantly increased compared to the HFD group. The liver thiobarbituric acid reactive substances was significantly lower in the PCA group than the HFD group. HFD-induced DNA damage in hepatocytes, as measured by comet assay, decreased in the PJ, AT, and PCA-supplemented groups. The PCA group exerted a superior antigenotoxic effect compared to other treatments. PCA recovered the concentration of plasma adiponectin, which was reduced by HFD. Adipocyte surface area (%) was significantly higher in the HFD group than the ND group, significantly lower in the PJ and PCA groups than the HFD group, and not significantly different compared with the ND group. Based on the results, supplementation of PJ, CT, AT, and PCA exhibited lipid-lowering effects in adipocytes of HFD-induced obese rats. Furthermore, the PCA group exhibited superior antioxidant activity in all treated groups. This study suggests that a mixed beverage consisting of PJ, CT, and AT may be a significant source of natural antioxidants, which might be helpful in preventing obesity and progress of various oxidative stresses induced by HFD.